Ethanol in alcoholic beverages is consumed regularly by about half of all adults and is the most frequently abused drug worldwide. Alcohol abuse results in substantial morbidity and mortality with the associated costs of medical care, accidents and lost productivity. State laws restrict driving under the influence of alcohol and many employees in safety-sensitive jobs, including school bus drivers, mass transit operators and commercial drivers, are prohibited from performing their jobs with blood alcohol levels above 0.04 g % or within four hours of consuming alcohol.
Ethanol distributes evenly throughout body fluids with the ethanol concentration proportional to the body fluid's water content. A single ethanol dose (1 g/kg body weight) raises the blood-alcohol level from the normal endogenous ethanol concentration of about 0.00015 g/dl to about 0.1 g/dl in about an hour on an empty stomach (Baselt, R. & Cravey, R., Deposition of Drugs and Chemicals in Man, 4th ed., p. 293, Chemical Toxicol. Inst., 1994). During the post-absorption phase, the ratio of ethanol in urine compared to whole blood averages 1.3, whereas the breath to whole blood ratio averages about 2180 and is related to the partition coefficient between blood alcohol in the lungs and alcohol vapor in air (Payne, J. P. et al., Nature 217:963, 1968; Heise, A. H., J. For. Sci. 12:454, 1967; Jones, A. W., J. Stud. Alc. 39:1931, 1978).
Alcohol in body fluids is commonly measured in a laboratory or in the field using enzyme assays, immunoassays, gas chromatography (GC), chemical oxidation and photometry, electrochemical oxidation with fuel cells, infrared spectrometry or solid-state semiconductor sensing. Breath and saliva ethanol measurements are commonly used for non-invasive instantaneous analysis and monitoring of alcohol use (Jones, A. W., J. Ann. Tox. 19:169, 1995). These methods provide an instant measurement of body fluid ethanol at the sampling time and are useful for determining the subject's condition at the specimen collection time, but provide no information on the subject's long-term or cumulative alcohol consumption. This is because the ethanol half-life in the body is relatively short, averaging 8 hr in breath, blood and urine (Baselt, R. & Cravey, R., Deposition of Drugs and Chemicals in Man, 4th ed., Chemical Toxicol. Inst., 1994). Thus, instantaneous measurements provide no information on alcohol use unless the sample is collected shortly after consumption.
Individuals who abuse alcohol often underreport the amount they consume. Moreover, blood carbohydrate-deficient transferins (CDT) that correlate with chronic alcohol abuse are only detected after relatively extreme levels of ethanol consumption (Bean, P. et al., Clin. Chem. 41(6):858, 1994). Thus, methods for monitoring long-term abstinence or limited alcohol consumption are needed for monitoring compliance with forensic and/or treatment programs.
Biological analytes can exit the body in either insensible or sensible perspiration. Insensible perspiration results from passive diffusion of water and other volatiles through the skin. Insensible perspiration varies with location on the body and skin temperature but is relatively similar on the upper arms, back, and lower chest. In contrast, sensible perspiration is actively secreted from eccrine and apocrine sweat glands (located, respectively, throughout the skin and in the axilla, pubic and mammary areas).
Many drugs, including ethanol, are excreted in sweat (Nyman, E. & Palmlov, A., Scand. Arch. Physiol. 74:155, 1936). During absorption, alcohol concentration of insensible sweat lags behind that of blood and breath but after complete absorption, the ethanol concentrations in insensible perspiration, breath and blood are similar. At the beginning of the post-absorption phase, when blood and breath levels begin to drop, the alcohol concentration of insensible sweat is slightly higher. During post-absorption, the alcohol elimination rate constant from skin is similar to that of blood and breath (Brown, D., Meth. Find. Exptl. Clin. Pharmacol. 7(5):269, 1985; Brown, D., Meth. Find. Exptl. Clin. Pharmacol. 7(10):539, 1985).
Because perspiration can be collected noninvasively, it is preferable to blood collection, an invasive procedure, or urine collection which involves privacy concerns and samples that can be readily adulterated. Collecting perspiration samples for analyte analysis is known. For example, clothing worn by an individual can be extracted and analyzed for drugs (Smith et al., J. Forensic Sci. 36:582-585, 1981; J Forensic Sci. 31:1269-1273, 1986). Perspiration induced by exercise, thermal stress or pilocarpine iontophoresis (a procedure involving small amounts of electrical current) can be collected and analyzed. A sensor placed on the skin and attached to a battery-operated device can electrochemically measure and record the skin ethanol vapor concentration every two to five minutes (Swift, R. M., et al., Alcoholism: Clin. Exp. Res. 16(4):721, 1992).
Occlusive dermal patches for collecting and retaining perspiration and analytes therein have been used to monitor exposure to chemicals including alcohol as described in U.S. Pat. No. 4,329,999, U.S. Pat. No. 4,732,153 and U.S. Pat. No. 5,396,901. These occlusive transdermal dosimeters utilize a waterproof dermal adhesive patch for collecting, storing and processing perspiration.
Occlusive dermal patches to collect perspiration generally have significant disadvantages. Hydration alters the skin's steady-state pH, affects transepidermal water loss and carbon dioxide emission rates, promotes growth of microbial species that colonize the skin and results in skin irritation. After three to five days, the pH of skin, the transepidermal water loss and carbon dioxide emission rates, and the number of microbes under an occlusive patch all increased significantly (Aly, Raza et al., J Invest. Dermatol. 71(6):378-381, 1978; Aly, Raza, et al., Am. J Infec. Control 16(3):95-100, 1988). In some cases, antifungal and antimicrobial agents have been included in occlusive patches to inhibit microbial growth and glycolysis by microbes growing in or under the patch (U.S. Pat. No. 4,329,999 and U.S. Pat. No. 4,732,153). Perspiration also tends to leak from some occlusive patches affecting analyte analysis results.
Carbon (e.g., activated charcoal) has been used to selectively adsorb volatile solutes in gas or liquid that contacts the carbon particles. Charcoal is activated by exposing it to high temperatures in a controlled atmosphere to produce microscopic pores in the carbon crystalline lattice. These pores are responsible for adsorption of compounds.
Some dermal patches have included activated charcoal as a binding material. For example, U.S. Pat. No. 4,732,153 discloses a transdermal dossier to monitor exposure to chemical agents by providing an unbroken fluid link between tissue fluids in the skin and the fluid collecting component which may include activated charcoal as a binding material. Similarly, U.S. Pat. No. 5,396,901 describes a watertight transdermal dossier connected by a fluid bridge to the skin for storing collected fluid and chemical substances in a tamper-resistant container. U.S. Pat. No. 4,756,314 describes an osmotically-driven absorbent sweat collection pad, which may contain activated charcoal, in a patch that stores fluid phase water and substances in perspiration for determining the presence of low molecular weight substances in sweat. U.S. Pat. No. 4,909,256 discloses a transdermal patch that includes a charcoal-containing binding reservoir in an airtight adhesive cover for monitoring exposure to chemical substances including ethanol. U.S. Pat. No. 4,960,467 describes an occlusive patch for collection of liquid transdermal substances in a wettable substance binding reservoir of activated charcoal powder immobilized in a gel matrix.
Carbon-containing wound dressings are also known. These include KALTOCARB.TM. (Britcair), made of alginate and charcoal; OPRASORB.TM. (Lohmann GmbH & Co. KG, Nuweid, Germany), an activated charcoal cloth; and LYOFOAM.TM. (Seton Healthcare), a charcoal-containing polyurethane foam (Dover et al., Brit. J Plastic Surgery 48:230235, 1995; Wollina et al., Skin Pharmocol. 9:35-42, 1996).
Dermal patches that collect components of perspiration have been described in U.S. Pat. No. 5,203,327 and U.S. Pat. No. 4,957,108, both hereby incorporated by reference.
The non-occlusive dermal patch of the present invention overcomes many of the disadvantages associated with other transdermal patches and methods of monitoring alcohol consumption. This dermal patch collects and retains volatile alcohol in vapor phase perspiration during the entire period the patch is worn, thus providing a system of monitoring ethanol consumption for over a week without collecting and storing liquid perspiration or causing skin irritation.